Acute and chronic post-infarction ischemic heart failure in humans is characterized by myocardial regeneration which is limited to the myocyte compartment of the surviving myocardium (259-270). Additionally, small areas of spontaneous myocardial regeneration which invade the infarct shortly after the ischemic event have been identified (267). In addition to the loss in muscle mass, the coronary vasculature remains defective and the extent and regulation of myocardial perfusion are severely impaired (271-281). Alterations in the balance between oxygen demand and supply have been viewed for a long time as critical determinants of the evolution of the ischemic myopathy (282). Pathology of the coronary circulation together with humoral, mechanical and biochemical factors sustain the ischemic myopathy and condition its unfavorable progression to terminal failure (283-288).
Despite advances in understanding the etiology of coronary artery disease (CAD) together with early diagnosis of pre-clinical atherosclerotic lesions and treatment of conventional risk factors, cardiovascular disease continues to be the leading cause of death in the industrialized world (289). Coronary atherosclerosis is the result of the evolving and complex interplay of endothelial injury, inflammatory mediators and the accumulation of oxidized lipids within the arterial wall (290-292). The presence of pro-inflammatory and anti-inflammatory cytokines mediates the cross-talk between the injured endothelial cells and the constituents of the vessel wall which condition the progression of the atherosclerotic plaque (292-296). The site of coronary artery stenosis is characterized by a large fibrous cap, a small lipid core and calcification; vessel pathology typically shows inward growth and narrowing of the lumen. Conversely, non-constrictive coronary atherosclerosis manifests itself with a lipid deposition and a thin fibrous cap without a change in vessel luminal diameter (291). However, it is the latter which is commonly involved in the initiation of an acute coronary syndrome triggered by thrombosis secondary to plaque rupture or erosion (297-299). More than 50% of these events occur in the proximal portion of the epicardial coronary arteries (300) resulting in sudden death, myocardial infarction or ischemic cardiomyopathy.